Rescue of in vitro models of CSF1R-related adult-onset leukodystrophy by iluzanebart: mechanisms and therapeutic implications of TREM2 agonism by Kelley C. Larson, Frederick W. Gergits, Abigail J. Renoux, Elizabeth J. Weisman, Borislav Dejanovic, Liyue Huang, Bhaumik Pandya, Donald G. McLaren, Berkley A. Lynch, Richard Fisher, Evan Thackaberry, David Gray, Francois Gaudreault, Christian Mirescu

“…Similar functions have also been ascribed to triggering receptor expressed on myeloid cells 2 (TREM2), which shares an analogous microglia enrichment profile and converging intracellular signaling pathway mediated by spleen associated tyrosine kinase (SYK) and phosphoinositide-3-kinase (PI3K). …”
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Functional Remediation Improves Serum BDNF and TrkB Levels in Euthymic Patients with Bipolar Disorder: A Randomized Trial Study by Li R, Li J, Ji SS, Li D, Chu L, Zhang J, Sun X, Luo X, Zhang Y

“…Ru Li,1,* Jiaxin Li,1,* Shiyi Suzy Ji,2 Dazhi Li,1 Lijun Chu,1 Jian Zhang,1 Xia Sun,1 Xingguang Luo,3 Yong Zhang1 1Unit of Bipolar Disorder, Tianjin Anding Hospital, Tianjin, People’s Republic of China; 2Department of Counseling and Clinical Psychology, Teachers College, Columbia University, NY, New York, USA; 3Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA*These authors contributed equally to this workCorrespondence: Yong Zhang, Unit of Bipolar Disorder, Tianjin Anding Hospital, 13 Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel/Fax +86 22 8818 8258, Email zhangyong@tjmhc.comPurpose: We aimed to verify the impact of functional remediation (FR) on serum brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) levels, to explore the biomechanism of FR intervention in patients with euthymic bipolar disorder (BD).Patients and Methods: This is a randomized controlled, 12-week intervention study with participants randomized into the FR group (n=39) and the treatment as usual group (TAU, n=42) at the 1∶1 ratio. 17-Hamilton Depression Rating Scale-17 (HDRS-17), Young Mania Rating Scale (YMRS), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to assess affective symptoms and cognitive functioning both at baseline and week 12, respectively. …”
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Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients by Rick Wilbrink, Stefan F.H. Neys, Rudi W. Hendriks, Anneke Spoorenberg, Frans G.M. Kroese, Odilia B.J. Corneth, Gwenny M.P.J. Verstappen

“…Next, we explored B cell subset distribution and B-cell receptor (BCR) signaling responses in circulating B cells from 28 r-axSpA patients and 15 HCs, by measuring spleen tyrosine kinase, phosphoinositide 3-kinase and extracellular signal regulated kinase 1/2 phosphorylation upon α-Ig stimulation using phosphoflow cytometry. …”
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The suppression of the SPHK1/S1P/S1PR3 signaling pathway diminishes EGFR activation and increases the sensitivity of non-small cell lung cancer to gefitinib by Jing Zhang, Zequn Wang, Xihua Wei, Mengyuan Han, Ribai Yan, Lijie Ma, Yan Pan

“…Several studies have indicated that sphingosine kinase 1 (SPHK1) plays a regulatory role in epidermal growth factor receptor (EGFR) signaling, and its elevated expression may be associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Furthermore, the catalytic product of SPHK1, sphingosine 1-phosphate (S1P), along with its receptor, sphingosine 1-phosphate receptor 3 (S1PR3), plays a regulatory role in the function of the EGFR. …”
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The prognostic value of systemic immune-inflammation index in patients with unresectable hepatocellular carcinoma treated with immune-based therapy by Tian He, Bin Xu, Lu-Na Wang, Zi-Yi Wang, Huan-Chen Shi, Cheng-Jie Zhong, Xiao-Dong Zhu, Ying-Hao Shen, Jian Zhou, Jia Fan, Hui-Chuan Sun, Bo Hu, Cheng Huang

“…A training cohort of 93 patients received atezolizumab plus bevacizumab (T + A), while a validation cohort of 175 patients underwent treatment with tyrosine kinase inhibitors (TKIs) combined with anti-PD-(L)1 therapy. …”
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The Potential Role of sPD-L1 as a Predictive Biomarker in EGFR-Positive Non-Small-Cell Lung Cancer by Vesna Ćeriman Krstić, Dragana Jovanović, Natalija Samardžić, Milija Gajić, Jelena Kotur Stevuljević, Aleksandra Klisic, Ivan Soldatović, Damir Radončić, Marina Roksandić Milenković, Biljana Šeha, Nikola Čolić, Katarina Lukić, Milan Savić

“…Materials and Methods: Blood samples from 35 patients with EGFR-mutated (EGFRmut) adenocarcinoma who achieved disease control with EGFR tyrosine kinase inhibitor (EGFR TKI) therapy were collected for sPD-L1 analysis. …”
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Molecular docking and dynamics studies to identify novel active compounds targeting potential breast cancer receptor proteins from an indigenous herb Euphorbia thymifolia Linn [ver... by ShamaPrasada K, Reshma Kumarchandra, Vasavi Kumblekar, K Sreedhara Ranganath Pai, Suman Manandhar, Sharada Rai, Rajeshwari Shastry

“…Methods ME.ET was subjected to GC-MS analysis to screen the phytoconstituents, and the identified compounds were docked with protein targets such as extracellular signal-regulated kinases (ERK1), a serine/threonine kinase-1(AKT1), human epidermal growth factor 2 (HER2), estrogen receptor (ER), maternal embryonic leucine zipper kinase (MELK), polo-like kinase-1(PLK1), and protein tyrosine kinase (PTK6). Compounds with good docking scores were further subjected to dynamic studies to understand the protein ligand binding stability, ligand pathway calculation, and molecular mechanics energies combined with Poisson-Boltzmann (MM/PBSA) calculations using the Schrodinger suite. …”
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Ibrutinib disrupts blood-tumor barrier integrity and prolongs survival in rodent glioma model by Sanghee Lim, Minhye Kwak, Jeonghan Kang, Melissa Cesaire, Kayen Tang, Robert W. Robey, William J. E. Frye, Baktiar Karim, Donna Butcher, Martin J. Lizak, Mahalia Dalmage, Brandon Foster, Nicholas Nuechterlein, Charles Eberhart, Patrick J. Cimino, Michael M. Gottesman, Sadhana Jackson

“…Ibrutinib, FDA-approved lymphoma agent, inhibits Bruton tyrosine kinase (BTK) and has previously been shown to independently impair aortic endothelial adhesion and increase rodent glioma model survival in combination with cytotoxic therapy. …”
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Serum Pharmacochemistry and Network Pharmacology Reveal Active Compounds and Mechanisms of the Huaxian Formula in Alleviating Radiation-Induced Pulmonary Fibrosis by Gong C, Chen J, Zou P, Fang Z, Quan L, Wang J, Yin J, Lin B, Lang J, Chen M

“…Overlapping these compounds with 991 RIPF-related genes yielded 127 genes primarily associated with the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and the MAPK signaling pathway. …”
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Radiogenomics and machine learning predict oncogenic signaling pathways in glioblastoma by Abdul Basit Ahanger, Syed Wajid Aalam, Tariq Ahmad Masoodi, Asma Shah, Meraj Alam Khan, Ajaz A. Bhat, Assif Assad, Muzafar Ahmad Macha, Muzafar Rasool Bhat

“…Disruptions in various oncogenic signaling pathways, such as Receptor Tyrosine Kinase (RTK)-Ras-Extracellular signal-regulated kinase (ERK) signaling, Phosphoinositide 3- Kinases (PI3Ks), tumor protein p53 (TP53), and Neurogenic locus notch homolog protein (NOTCH), contribute to the development of different tumor types, each exhibiting distinct morphological and phenotypic features that can be observed at a microscopic level. …”
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Overall Survival of Patients with Metastatic Renal Cell Carcinoma Following the Introduction of Targeted and Immunotherapies: A Norwegian Retrospective, Real-World Registry Data St... by Puco K, Notland CS, Szulkin R, Jonasson C, Beisland C, Johannesen TB, Solli O, Oldenburg J, Heinrich D

“…The results may provide additional information on the benefits of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in clinical practice.Patients and Methods: We performed a longitudinal, retrospective, non-interventional cohort study using data from four national registries. …”
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Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis by Shang‐Gin Wu, Chao‐Chi Ho, James Chih‐Hsin Yang, Shu‐Han Yu, Yen‐Feng Lin, Shu‐Chin Lin, Bin‐Chi Liao, Ching‐Yao Yang, Yen‐Ting Lin, Chong‐Jen Yu, Ya‐Ting Chuang, Wei‐Yu Liao, Kah Yi Yap, Weng Si Kou, Jin‐Yuan Shih

“…Abstract Background Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) remains a significant hurdle for patients with EGFR‐mutated non‐small cell lung cancer (NSCLC), particularly those lacking the EGFRT790M. …”
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Phase I study of pembrolizumab in combination with ibrutinib for the treatment of unresectable or metastatic melanoma by Yuan Yao, Yiyi Yan, Vera J. Suman, Allan B. Dietz, Courtney L. Erskine, Anastasios Dimou, Svetomir N. Markovic, Svetomir N. Markovic, Robert R. McWilliams, Heather N. Montane, Matthew S. Block, Matthew S. Block

“…The small molecule ibrutinib is a dual-target agent that inhibits Bruton’s Tyrosine Kinase (BTK) and Interleukin-2-inducible T-cell Kinase (ITK), a key regulator of Th2 immunity. …”
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A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings by Steven P. Treon, Camille N. Kotton, David J. Park, Giorgia Moranzoni, Camilla K. Lemvigh, Joseph C. Gathe, Tilly A. Varughese, Christopher F. Barnett, Johnny M. Belenchia, Nina M. Clark, Charles M. Farber, Muhammad Bilal Abid, Gulrayz Ahmed, Christopher J. Patterson, Maria L. Guerrera, Jacob D. Soumerai, Vipheaviny A. Chea, Isabel P. Carulli, Jackson Southard, Shuqiang Li, Catherine J. Wu, Kenneth J. Livak, Eric Holmgren, Pil Kim, Carrie Shi, Holly Lin, Vanitha Ramakrishnan, Ying Ou, Scott Olszewski, Lars Rønn Olsen, Derin B. Keskin, Derin B. Keskin, Zachary R. Hunter, Christopher Tankersley, Todd Zimmerman, Binod Dhakal

“…BackgroundCytokine release triggered by a hyperactive immune response is thought to contribute to severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2)–related respiratory failure. Bruton tyrosine kinase (BTK) is involved in innate immunity, and BTK inhibitors block cytokine release. …”
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RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer by Charlotte K. Kindt, Sidse Ehmsen, Sidse Ehmsen, Sidse Ehmsen, Sofie Traynor, Benedetta Policastro, Nikoline Nissen, Mie K. Jakobsen, Monique F. Hundebøl, Lene E. Johansen, Martin Bak, Elsa Arbajian, Johan Staaf, Henrik J. Ditzel, Henrik J. Ditzel, Henrik J. Ditzel, Carla L. Alves

“…High expression of the receptor tyrosine kinase REarranged during Transfection (RET) has been associated with resistance to endocrine therapy in breast cancer, but the role of RET in CDK4/6i treatment response/resistance remains unexplored.MethodsTo identify gene expression alterations associated with resistance to combined endocrine therapy and CDK4/6i, we performed RNA sequencing of two ER+ breast cancer cell models resistant to this combined therapy. …”
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